Lately, in our country, it causes trouble that androgen dependent diseases such as prostatic cancer and benign prostatic hyperplasia, and estrogen dependent diseases such as mammary cancer and endometriosis, are increasing in the morbidity. For example, the percentage of mortality of the prostatic cancer was 3.9 men per 100,000 of population by statistical data in 1984, and was about 1/10 of the non Caucasian men in the Western country. However, it is increasing gradually by prolonging life due to improvement of medical treatment and western diet. In 1993, that percentage is 6.7 men per 100,000 of population and it is coming to European and U.S. levels. It is expected that the numbers of mortality based on the prostatic cancer in 2015 will be four times more of those in 1990. This is the worst increasing percentage in all cancers.
It has become clear from many views that subjective conditions and objective conditions of the androgen dependent diseases will be improved by depressing the androgen levels in blood. Therefore, treatment of these diseases have been accomplished by lowering the androgen in blood by castration, by administering an agonist of the LH-RH to lower the androgen in blood to the castration level, and by administering anti-androgen agents antagonizing an androgen receptor to control the action of the androgen. In fact, the clinical effects are broadly noticed. However, since the castration causes a lowering of QOL, it is only proceeded in very limited diseases. The agonist of LH-RH has problems; side effect such as a bone pain or dysuria caused by a phenomenon peculiar to the agonist (temporary increase of the androgen), and rekindling for continuous existence of androgen originated from adrenal glands. Further, it is indicated that the effect of the anti-androgen agents is decreased by the development of variants of the androgen receptor during the medicine is administered. Therefore, "a method of complete blockage of the androgen" is prescribed for more effective endocrine therapeutics. The method is aimed to completely inhibit the androgen in blood by combination of several endocrine treatment methods, and more effective treatment is expected.
Testosterone exhibiting the most effective androgen activity in C19 steroids having androgenic activity can be synthesized with 17.beta.-HSD from a substrate of andorostendione. By inhibiting this 17.beta.-HSD, the concentration of testosterone in blood is directly lowered, so that it is expected to effectively treat the above androgen dependent diseases. In addition, since this enzyme is also a biosynthetic enzyme of estoradiol having the highest estrogen activity in C.sub.18 steroid having estrogenic activity, it is also expected to effectively treat the estrogen dependent diseases such as mammary cancer and endometriosis.
Steroid compounds and non-steroid compounds have been proposed as 17.beta.-HSD inhibitors. As the non-steroid compounds, for example, flavons and isoflavons, which are described in Biochemical and Biophysical Research Communications, Vol. 215, 1137-1144 (1995), and fatty acids, which are described in Journal of Steroid Biochemistry, Vol. 23, 357-363 (1985), are known. However, since the activity of these compounds is not satisfied, it is expected to obtain materials having higher activity.